Safety Alert by the U.S. Food and Drug AdministrationTerbutaline: Label Change - Warnings Against Use for Treatment of Preterm Labor

Commentary by Lawrence P. Kaplan, PhD

It all started nineteen years ago on a bright sunny warm Florida day. My wife, Gail, had been on bed rest since the 27th week of the twin pregnancy. On Tuesday, February 25, 1992, the physician instructed her to enter the hospital since she had been dilating. After continuous hospital monitoring, three days after admission, the physician attempted to prevent her pre-term labor by treating her first with Magnesium Sulfate, then Terbutaline. The boys would be born 23 days later; all three exposed to daily bolus injections of Terbutaline. (Click here to read a transcript of a 2005 interview on the effects of Magnesium Sulfate and Terbutaline).

"I confess that I have prescribed magnesium sulfate tocolysis to dozens of women. I also am committed to changing my practice pattern in regard to this agent.”—Robert L. Barbieri, MD, Chairman, Obstetrics and Gynecology, Brigham And Women's Hospital, a teaching affiliate of Harvard Medical School

Last week, the FDA issued the following statement: “FDA notified healthcare professionals that injectable terbutaline should not be used in pregnant women for prevention or prolonged treatment (beyond 48-72 hours) of preterm labor in either the hospital or outpatient setting because of the potential for serious maternal heart problems and death. In addition, oral terbutaline should not be used for prevention or any treatment of preterm labor because it has not been shown to be effective and has similar safety concerns. Death and serious adverse reactions, including increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia have been reported after prolonged administration of oral or injectable terbutaline to pregnant women.”

"oral terbutaline should not be used for prevention or any treatment of preterm labor because it has not been shown to be effective and has similar safety concerns"—FDA

“Terbutaline is approved by the FDA to treat airway restriction caused by asthma, bronchitis and emphysema. However, the drug is also popular among obstetricians and gynecologists to prevent preterm labor or to treat preterm labor that lasts for more than 48 hours. This off-label use has never been green-lighted by the FDA,” (Aboutlawsuits.com). WebMD.com refers to the term off-label as unlabeled use. “An unlabeled use of a drug is when a doctor prescribes a medication for a purpose other than that for which it has been specifically designed and approved. Sometimes a drug is prescribed for a specific unlabeled use so often that doctors consider it a common practice.”

This is not the first time the FDA has warned healthcare professionals about the serious adverse reactions to Terbutaline. “Dr. Stuart L. Nightingale, Associate Commissioner for Health Affairs at the FDA issued a statement on November 13, 1997 that said that the FDA would like to call to your attention concerns about subcutaneous administration, via infusion pump, of terbutaline sulfate for the treatment and prevention of preterm labor. The use of terbutaline sulfate to treat preterm labor is an unapproved or "off-label" use. No benefit from prolonged treatment has been documented. In addition, the safety of long-term subcutaneous administration of terbutaline sulfate, especially on an outpatient basis, has not been adequately addressed... The impact of long-term use on maternal glucose metabolism and the risks of prolonged exposure of the fetus are largely unknown." www.ncbi.nlm.nih.gov/books/NBK33241

The American College of Obstetricians and Gynecologists concluded in 2003 that “neither maintenance treatment with tocolytic drugs nor repeated acute tocolysis improve perinatal outcome; neither should be undertaken as a general practice”. www.guideline.gov/content.aspx?id=3993

Fetal and maternal tachycardia, due to terbutaline use, has been known since 1975. The side effects have been known for over 36 years.

According to Robert L. Barbieri, MD, Chairman, Obstetrics and Gynecology, Brigham And Women's Hospital, a teaching affiliate of Harvard Medical School, “A major problem is that most clinical trials that examine tocolysis have significant flaws, which limits the strength of the findings. I confess that I have prescribed magnesium sulfate tocolysis to dozens of women. I also am committed to changing my practice pattern in regard to this agent.”

So here we are fourteen years later after Dr. Nightingale issued a statement of concerns about terbutaline use for prevention of preterm labor. The side effects have been known for over 36 years. I always wondered why Baby B’s heart rate would increase to over 180 beats per minute after each dose of Terbutaline. I would just shutter every time Gail received an automatic dose of Terbutaline.

And now for the rest of the story… In 2005, I was interviewed by Teri Arranga of AutismOne radio.

Click here to read the transcript of the 2005 interview that includes information about the studies conducted by researchers from Johns Hopkins University and Duke University.

These comments do not necessarily reflect the views of US Autism & Asperger Association.